A Specialized Program of Research Excellence for patients with cancer of the head and neck entitled The Molecular Basis of Head and Neck Biology, Treatment and Prevention is proposed that will significantly improve treatment results and reduce morbidity and mortality associated with this devastating malignancy. These goals will be achieved through improved understanding and application of molecular biology to the detection, prevention, treatment selection and development of new therapies for patients with head and neck cancers. Our ongoing hypothesis is that increased understanding of the molecular basis for treatment will allow more precise individualized patient selection that will result in less morbid therapy and improved quality of life, in addition to the possibility of better control of metastases and earlier detection or prevention of second primary malignancies. We propose continuation of this integrated translational research program consisting of four major projects that explore 1.) more specific treatment selection for patients likely to be cured with radiation or chemotherapy; 2.) new small molecule inhibitors of apoptosis-regulation to increase chemo/radiosensitivity; 3.) improved survival through development of sound prevention strategies; and 4.) the role of critical small molecules and chemoradiation sequencing for optimizing treatment results. These major translational projects are complemented by ongoing highly successful Career Development and Developmental Research Programs. All SPORE studies are supported by three Core Resources with demonstrated success in our initial funding period (Administration and Translational Trials Support, Biostatistics, and Tissue and Histopathology). Emphasis is placed on continued ongoing scientific review of all programs and core resources through utilization of an established Operations Committee, Senior Advisory Council and External Review Committee comprised of expert basic and clinician scientists in the field of cancer research. Strong institutional commitment in our initial funding period has been increased significantly in this renewal application to support equipment needs, our Developmental Research Program and provide increased flexibility to pursue further investigations of novel discoveries that are made as a result of these SPORE projects and collaborations. This Head and Neck SPORE is a fully integrated component of the University of Michigan Comprehensive Cancer Center. We have incorporated extensive use of Cancer Center core facilities and clinical and laboratory resources, and we draw heavily on experienced Cancer Center leadership. Superb teams of experienced clinical / basic collaborators combined with high institutional commitment and priority, and extensive patient resources provide an outstanding research environment that will ensure continued success in achieving overall SPORE goals.